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The clinical inadequacy of the concept of treatment-resistant depression: Innovative strategies in assessment and psychotherapeutic management

Jenny Guidi, Giovanni A. Fava

2025Clinical Psychology Review9 citationsDOIOpen Access PDF

Abstract

Pharmacological strategies have been developed for patients with major depressive disorder who fail to respond to standard drug treatment. The current clinical approach primarily relies on counting episodes that fulfill specific criteria and regards non-pharmacological strategies as of marginal value, despite their recognized importance in treating depression. Most attention is devoted to treatment-resistant patients' characteristics rather than to the process related to therapeutic management. However, how the patient experiences the treatment process, his/her interaction with the physician/therapist and significant others, and the patient's role in treatment plan (self-management) are all essential therapeutic components. A broader evaluation of factors related to the patient (e.g., illness denial, psychological reactance, demoralization), the therapy (e.g., clinician's attitude, behavioral toxicity of antidepressants), the environment (e.g., allostatic load/overload and health-damaging behaviors), and morbidity (e.g., medical and psychiatric comorbidity) is warranted. Assessment based on clinimetric methods (i.e., staging, macro-analysis) and clinical judgment allow a differential diagnosis of phenomena such as non-response, pseudo-resistance, treatment resistance, loss of clinical effect during maintenance antidepressant treatment, failure to achieve remission after a psychotherapy trial, partially remitted depression (i.e., presence of residual symptoms). Choice of the psychotherapeutic approach for treatment-resistant depression (TRD), particularly cognitive-behavioral therapy, mindfulness-based cognitive therapy and interpersonal psychotherapy, should follow the indications derived from clinical assessment. Treatment of TRD can thus be conceptualized as an integrated therapeutic approach to different components encompassing symptoms, psychosocial factors, lifestyle and psychological well-being.

Topics & Concepts

PsychologyDepression (economics)PsychotherapistClinical psychologyEconomicsMacroeconomicsTreatment of Major DepressionMental Health Research TopicsMental Health Treatment and Access
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